DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-13, in the reply filed on 05/15/2026 is acknowledged.
Claim 14 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/15/2026.
Status of the Claims
Claims 1-14 are currently pending.
Claim 6 and 13 are amended.
Claim 14 has been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 1-13 have been considered on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the transmembrane domain" in line 4. There is insufficient antecedent basis for this limitation in the claim. Dependent claims 2-13 are included in this rejection due to dependency.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 6-9, and 11-13 are rejected under 35 U.S.C. 102(a)(1) and/or 102(a)(2) as being anticipated by Shum et al (US 20190183936 A1).
With regards to claim 1, Shum teaches a chimeric cytokine receptor comprising a ligand binding region consisting of a cytokine-binding region of a cytokine receptor ([0049]), and a T-cell activating region comprising a transmembrane domain ([0071]) and the intracellular domain of an IL-7 receptor alpha chain ([0049]). Shum teaches that the transmembrane domain has an insertion of the instant SEQ ID NO: 5 between positions 244 and 245 in the amino acid sequence of SEQ ID NO: 1 (See [0077], specifically SEQ ID NO: 24 of Shum). Shum teaches that the transmembrane domain has an insertion of the instant SEQ ID NO: 2 between positions 243 and 244 in the amino acid sequence of SEQ ID NO: 1 (See [0077], specifically SEQ ID NO: 23 of Shum). Shum also teaches that the transmembrane domains are mutations provided to the wild-type IL-7Ralpha which is the instant SEQ ID NO: 1 ([0077]-[0078]).
Regarding claim 6, Shum teaches the chimeric cytokine receptor of claim 1 in the form of a nucleic acid encoding the chimeric cytokine receptor ([0086]).
Regarding claim 7, Shum teaches a gene expression vector comprising the nucleic acid of claim 6 which allows for the expression thereof ([0086]).
Regarding claim 8, Shum teaches a host cells comprising the gene expression vector of claim 7 ([0086]).
Regarding claim 9, Shum teaches that the host cell further comprises a chimeric antigen receptor within the expression vector which comprises a base sequence encoding a CAR allowing for the expression thereof ([0088]-[0089]).
Regarding claims 11-12, Shum teaches that the host cell is an immune cell, specifically a T cell, an NK cell or a macrophage ([0155] and [0087]).
Regarding claim 13, Shum teaches a cell preparation of the host cell ([0029] and Fig. 7).
Therefore, Shum anticipates the claims.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Shum et al (US 20190183936 A1), as applied to claims 1, 6-9, and 11-13 above, and in view of Taunton et al (US 20170306303 A1).
With regards to claims 2-3, the limitations of the independent claim 1 are taught above.
Shum does not teach that the cytokine receptor is selected from the group consisting of IL-6 receptor, IL-1 receptor type 2, a GM-CSF receptor alpha chain or a GM-CSF receptor beta chain as required by claim 2. Further, Shum does not teach that the cytokine receptor is a IL-6 receptor and further comprises the ligand-binding region of gp103 as required by claim 3.
However, Taunton teaches various embodiments of engineered receptor type molecules which are conditionally active as a method of controlling the engineered receptors. Taunton teaches that the cell surface receptors employed may include cytokine receptors ([0688]). Taunton teaches that conditionally active engineered receptors are beneficial to modulate immune cell activation as compared to traditional CAR and engineered T cell receptors because they are able to be inactivated when stimulation is unwanted, undesirable or no longer necessary.
Regarding claim 2, Taunton teaches that the cytokine receptor can be chosen from IL-6 family receptors ([0688]/[0691]).
Regarding claim 3, Taunton teaches that the cytokine receptor can be IL-6 receptor beta subunit, otherwise known in the art as the portion of the IL-6 receptor which binds glycoprotein 130 (gp130) ([0691]).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the chimeric cytokine receptor taught by Shum with the cell surface cytokine receptors taught by Taunton to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Taunton teaches the ability to employ a wide range of cytokine receptors successfully because their conditionally active engineered receptors are beneficial to modulate immune cell activation as compared to traditional CAR and engineered T cell receptors because they are able to be inactivated when stimulation is unwanted, undesirable or no longer necessary ([0004]). One of ordinary skill in the art would have a reasonable expectation of success when combining Shum with Taunton because Shum and Taunton teach the necessary steps to employ various cytokines as engineered receptors.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Shum et al (US 20190183936 A1), as applied to claims 1, 6-9, and 11-13 above, and in view of Cui et al (Jour. Of Immunol., 2019).
With regards to claims 4-5, the limitations of the independent claim 1 are taught above.
Shum does not teach that the chimeric cytokine receptor has a mutation which reduces the activity of one or more motifs selected from the group consisting of a JAK-binding motif, a STAT3 association motif, and a STAT5/PI3K association motif which are contained in said intracellular domain as required by claim 4. Shum does not teach wherein said mutation is a Y449F, M452L or Y456F in the amino acid sequence of SEQ ID NO: 1 as required by claim 5.
Shum does teach that STAT5 is constitutively active in the cells transduced with the IL-7R cytokine receptor ([0026]).
However, Cui teaches about IL-7R dependent modulation of T cell development and homeostasis (abstract). Cui teaches that peripheral T cell numbers increase in M452L mutation mice with enhanced survival and homeostatic proliferation (abstract).
Regarding claims 4-5, Cui teaches two IL-7R (SEQ ID NO: 1) mutations: Y449F and M452L (abstract). Cui teaches that the Y449F mutation demonstrated decreased PI3K and STAT5 signaling and that the M452L mutation demonstrated decreased PI3K signaling (abstract).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the chimeric cytokine receptor taught by Shum with the mutations taught by Cui to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Cui teaches that peripheral T cell numbers increase in M452L mutation mice with enhanced survival and homeostatic proliferation (abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Shum with Cui because Shum teaches the necessary information to produce a chimeric cytokine receptor T-cell and Cui teaches the necessary steps to mutate the IL-7R for modulation of T cell proliferation.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Shum et al (US 20190183936 A1), as applied to claims 1, 6-9, and 11-13 above, and in view of Garlanda et al (Immunity, 2014).
With regards to claim 10, the limitations of the independent claim 1 are taught above.
Shum does not teach that the host cell of claim 8 further comprises an IL-1 receptor type II expression vector which comprises a base sequence encoding a full-length IL-1 receptor type 2 in a state which allows for the expression thereof as required by claim 10.
Shum does teach that the cell containing the chimeric cytokine receptor may additionally include a decoy receptor as an additional exodomain ([0010]). Further, Shum teaches that the decoy receptor may lack signal transmission activity ([0015]). Shum also teaches that the decoy receptor exodomain may be of an inhibitory receptor normally expressed by T cells ([0020]).
However, Garlanda teaches about the IL-1 receptor type II (IL-1R2). Garlanda teaches that IL-1R2 is a decoy receptor which negatively regulates IL-1 activity by acting as a molecular trap for IL-1 (pg. 9, para 4). Garlanda teaches that the IL-1R2 receptor is normally expressed by monocytes, polarized M2 macrophages, microglial cells, neutrophils, B cells, and T regulatory (Treg) cells (pg. 9, para 5). Finally, Garlanda teaches that IL-1R2 expression both increases anti-inflammatory effect and is enhanced by anti-inflammatory signals (pg. 9, para 6).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the chimeric cytokine receptor optionally including a decoy receptor taught by Shum with the IL-1R2 decoy receptor taught by Garlanda to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Shum teaches the optional incusion of a decoy receptor which is already normally expressed on T cells and Garlanda teaches that the IL-1R2 is a decoy receptor normally expressed on T cells (see Garlanda pg. 9, para 4-6). One of ordinary skill in the art would have a reasonable expectation of success when combining Shum with Garlanda because Shum teaches the necessary information to produce a chimeric cytokine receptor T-cell optionally including a decoy receptor and Garlanda teaches the necessary that IL-1R2 is a decoy receptor normally found on certain T cells.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
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